Polyphenolic natural products are of current interest because of their numerous biological activities, their widespread occurrence in foodstuffs, and their resulting relevance for human health. Polyphenolic natural products have one or several hydroxyl groups on their aromatic rings and often an additional hydroxyl group in the 3 position. Several different hydroxylation patterns of the A and B rings have been found in nature. Representative examples include: (−)-epiafzelechin, (+)-catechin, (−)-epicatechin, (−)-gallocatechin, (−)-epigallocatechin, their respective 3-gallate esters, as well as two 3-(30-methyl)gallate esters, which are referred to collectively herein as “catechins.” (+)-Catechin, (−)-catechin, (+)-epicatechin and (−)-epicatechin are flavan-3-ols, with (+)-catechin, (−)-epicatechin the most abundant. Catechins constitute about 25% of the dry weight of fresh tea leaves although the total content varies widely depending on tea variety and growth conditions. Catechins are also present in the human diet in chocolate, fruits, vegetables and wine. Catechins have found use in the treatment of acute coronary syndromes, including but not limited to myocardial infarction and angina; acute ischemic events in other organs and tissues, including but not limited to renal injury, renal ischemia and diseases of the aorta and its branches; injuries arising from medical interventions, including but not limited to coronary artery bypass grafting (CABG) procedures and aneurysm repair; cancer; and metabolic diseases, including but not limited to diabetes mellitus. Health benefits of catechins have been broadly attributed to antioxidant properties, effects on intestinal microorganisms and nutrient absorption, and effects on metabolism and metabolic enzymes.
Catechins for use as pharmaceutical and neutraceutical preparations have been obtained through plant extraction, followed if desired by purification of individual catechin species using chromatographic methods. To prove definitively the structures and to develop structure-activity relationships assigned to the compounds purified from cocoa, and other sources, comparisons must be made of defined structure prepared synthetically to polyphenols such as epicatechin. Synthetic monomers, dimers and oligomers are useful in various in vitro and ultimately in vivo models for pharmacological activity.
From a purely synthetic viewpoint, however, such molecules present difficulty in controlling the desired stereochemistry, as well as the sensitivity of the unprotected compounds to acids, bases, and oxidizing agents. There are certain processes available for the synthesis of epicatechin, however, the processes and the starting material is very costly or final product is of very low yield, leading to a very costly final product. Therefore there remains a need for efficient synthetic processes for the large scale preparation of epicatechins and catechin monomers from commercially available sources.